Mutation and linkage analysis in genetic counseling for phenylketonuria in Kuwait

Phenylketonuria [PKU] is caused by mutations in the PAH gene. More than 250 PAH mutations have been identified, and their distribution among different populations varies significantly. Though PKU is prevalent in Kuwait, the molecular bases of the underlying genetic variants have never been studied. DNA from 20 PKU patients belonging to 11 families of Arabic origin as well as 30 healthy relatives was extracted using a 'salting-out' method. DNA samples were analyzed by polymerase chain reaction [PCR]/restriction fragment length polymorphism [RFLP] tests for 5 common PAH mutations [IVS10nt546, R261Q, IVS12nt1, IVS2nt1, R408W]. Linkage analysis and PAH haplotyping was carried out by the study of variable number tandem repeat and BglI, PvuII-a, PvuII-b, MspI, XmnI polymorphism by PCR or PCR/RFLP tests. Seven patients from 4 families were found to be homozygous for IVS10nt546, thus proving the frequency of this mutation among PKU chromosomes in Kuwait to be 36.4%. The four other PAH mutations were absent among the patients studied. The linkage analysis was informative in all but 1 of the families. Seven PAH haplotypes were identified among 22 PKU chromosomes from Kuwait. All the IVS10nt546 chromosomes had identical haplotype

delta ccr-5 mutation in the CCR-5 chemokine receptor gene conferring resistance to human immunodeficiency virus type 1: frequency in Kuwait

The homozygous deletion of 32 nucleotides in the CCR-5 gene [delta ccr-5] confers resistance to macrophage-tropic HIV-1. The aim of this study was to determine the frequency of delta ccr-5 in populations residing in Kuwait. A polymerase chain reaction [PCR] test for delta ccr-5 has been developed. The specificity of the test has been proved by direct sequencing of the PCR products amplified from individuals homozygous for the wild-type allele and from delta ccr-5/wild-type heterozygotes. Among 353 healthy individuals residing in Kuwait [270 Kuwaiti citizens and 83 Bedouins] tested for the delta ccr-5 mutation, 8 heterozygotes have been identified, 4 in each group. No homozygotes for the delta ccr-5 deletion have been found. The frequency of the delta ccr-5 allele in Kuwaiti nationals and Bedouins residing in Kuwait is 0.74 and 2.4%, respectively. The delta ccr-5 mutation is present in populations residing in Kuwait, though its frequency is quite low and can hardly influence the pace of HIV-1 spreading in Kuwait

Kuwaiti patient with osteopetrosis, renal tubular acidosis and cerebral Calcification is homozygous for a splice junction mutation in the carbonic anhydrase gene

Osteopetrosis, with renal tubular acidosis and cerebral calcification [ORTACC], is a rare genetic disorder caused by mutations in the carbonic anhydrase II [CAII] gene. Several CAII mutations have been reported, including a splice junction mutation in intron 2 in Arab patients from the Middle East and North Africa. Herein, we present our PCR/RFLP protocol for the diagnosis of this Arabic mutation and report its detection in a Kuwait patient with ORTACC

Molecular mechanisms of non-mendelian inheritance in genetic diseases

Recently identified molecular mechanisms [mitochondrial DNA mutations, genomic imprinting, uniparental disomy, unstable trinucleotide repeats] responsible for the non-mendelian patterns of some genetic diseases are reviewed. Among the diseases considered are LHON [Leber's hereditary optic neuropathy], MERRF [myoclonic epilepsy with ragged-red fibers], MELAS [mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes], Prader-Willi syndrome, Angelman syndrome, fragile-X syndrome, myotonic dystrophy, as well as others